Medicine Newbie: LDL structure

Showing posts with label LDL structure. Show all posts

Saturday, 26 February 2011

In blood circulation, TG and CE are packed into LDL particles forming a hydrophobic core surrounded by a surface monolayer of polar PL together with unesterified cholesterol (FC) and apoB. LDL normally also contains lipophilic antioxidants, mainly Vitamin E and ß-carotene. LDL is a large spherical particle, molecular weight of about 3 x 106 Da, with a diameter of 22-28 nm and density between 1.019-1.063 g/ml. The core is composed of some 1,600 molecules of CE (long chain fatty acid) and 170 molecules of TG. The CE is the main lipid of the lipoprotein core with the most fatty acyl chain in these esters being linoleate (Krieger et al. 1978). This core is shielded by a layer of PL (700 molecules), FC (600 molecules), and 1 molecule of apoB-100 (Steinberg 1997b, Stryer 1988, Yang et al. 1989). In the percent mass composition, each LDL particle consists of 35-45% CE, 7-10% FC, 7-10% TG, 15-20% PL, and 20-25% protein (Deckelbaum et al. 1987, Schultz and Liebman 1997).

Figure 2. Schematic model of LDL particle.

Overall structure of the LDL particle is shown in Fig. 2. The PLs are arrayed so that their hydrophilic heads are on the outside, allowing the LDL to be dissolved in the blood or intercellular fluid. Embedded in this hydrophilic coat is one apoB-100 molecule. Effective and efficient binding for apoB-100 to the LDL receptor is the prerequisite for cholesterol delivery into cells. In principle, LDL can also transport other lipophilic biosubstances into cells under the direction of apoB-100. On the other hand, apoB-100 gene mutation or conformational changes may affect LDL metabolism and plasma cholesterol levels (Innerarity et al. 1987, Aviram et al. 1988, Chen et al. 1994).

LDL structure (detailed)

Taken from: http://ethesis.helsinki.fi/

2.2.8. LDL composition, oxidizability, and endogenous antioxidants

In LDL particle, cholesteryl linoleate represents quantitatively the single most important polyunsaturated fatty acid (PUFA) which is the substrate for peroxidation. If PUFA becomes oxidized to lipid hydroperoxides, their isolated carbon-carbon double bonds are converted to conjugated double bonds showing a strong UV-absorption at 234 nm, designated as conjugated diene (CD) formation (Esterbauer et al 1993). Therefore, its content in LDL may influence the determination of oxidation resistance measured by CD or TBARS formation (Ziouzenkova et al. 1996).

Reaven et al. (1993) reported that LDL particles rich in PUFA are more readily oxidized than LDL particles enriched in saturated fatty acids or monounsaturated fatty acids. In addition, elevated levels of preformed lipid hydroperoxides and cholesterol in LDL were associated with increased oxidation susceptibility (Frei and Gaziano 1993). Studies have shown that monoenic fatty acids enriched LDL, for example oleic acid was remarkably resistant to oxidative modification as measured by decreased formation of CD and TBARS (Parthasarathy et al. 1990).

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitors reduced the susceptibility of LDL to oxidation by altering the LDL particle composition containing less lipid relative to protein (Lavy et al. 1991) or preserve endogenous antioxidants (Chen et al. 1997). In deed, most of these HMG-CoA reductase inhibitors themselves are antioxidants and could become bound to lipoprotein in the circulation to protect them against oxidation (Lennernas and Fager 1997, Girona et al. 1999).

LDL particle size could also influence its oxidation susceptibility. For example, small, dense LDL particles displayed diminished resistance to oxidative stress in vitro (Tribble et al. 1992, de Graaf et al. 1991).

Since LDL is the major extracellular transport vehicle for lipid-soluble antioxidants, it contains relatively large amounts of a-tocopherol, g-tocopherol, b-carotene, and ubiquinol-10 and among them a-tocopherol is the most important antioxidant known with 6 molecules per LDL particle (Esterbauer et al. 1995). As the oxidation goes on, a-tocopherol is the first and b-carotene is the last endogenous antioxidant in LDL particles to be depleted (Esterbauer et al. 1992).

The endogenous antioxidants contained in LDL particles might influence oxidation resistance (Tribble et al. 1994). Dietary antioxidant supplementation could increase their content in LDL and therefore, increase oxidation resistance of lipoproteins (Nyyssonen et al. 1994, Jialal et al. 1995). The composition of native LDL and the antioxidants contained in LDL are listed in Tables 2 and 3.

Table 2. Composition of human LDL